Trends in the diagnosis of Pneumocystis pneumonia
Keyword : Keywords: Pneumocystis jirovecii, pneumonia, respiratory specimens, microscopy, RSA, ELISA, Pneumocystis DNA, PCR
Author(s) : Elomba, C. Chidozie And Okonkwo, I.F
Abstract : Abstract Standard laboratory diagnosis of Pneumocystis pneumonia relies on microscopic visualization of stained causative agent P. jirovecii organisms or DNA detection by PCR in respiratory specimens. Since these specimens are obtained by invasive techniques that carry an associated risk of complications, and are not easy to perform in patients with respiratory failure or in children, development of a serological test is urgently needed to diagnose Pneumocystis pneumonia using minimally invasive samples like blood. Thus this review of trends in diagnosis of Pneumocystis pneumonia based on production of synthetic recombinant antigens (RSA) and development of an ELISA test. This innovative approach provides good insights on future serum testing for P. jirovecii pneumonia (PJP) diagnosis. Pneumocystis major surface glycoproteins (Msg) RSA-based ELISA that proved to have application as a serological approach for PJP diagnosis was designed and developed but its performance was not as good as intended, perhaps due to P. jirovecii evasion mechanism based on Msg antigenic variation. Thus, a new RSA based on the immunogenic behavior of P. jirovecii Kex1 protein was developed, which showed applicability in the detection of specific IgM anti-P. jirovecii antibodies when applied as an antigenic tool in LFIA techniques to study active PJP in human sera. Studies that presented diagnostic performance of a Kex1-based ELISA and their implications for future diagnostic studies on Pneumocystis pneumonia had revealed that Kex1 RSA-based IgM ELISA was successful in discriminating PJP and non- PJP patients, and that IgM levels significantly increased in patients with PJP. This indicated that Kex1 RSA-based ELISA has a high diagnostic potential and reinforces the idea that RSA is one of the most promising tools to achieve routine PJP sero-diagnosis, and will hopefully support the development of new studies that will focus on Kex1 RSA-based strategiesto validate and optimize a simpler, faster, and less-invasive diagnostic solutions. Moreover, detection of Pneumocystis DNA in clinical specimens using PCR assays has greatly improved PJP clinical diagnosis and epidemiology. The very sensitive and specific PCR tools have further allowed for accurate and early diagnosis of Pneumocystis infection, and sometimes revealed PJP in patients with negative microscopy test. Most patients with positive-PCR and negative-microscopy results were considered to be colonized by Pneumocystis organisms.